The use of combination chemotherapy has been developed successfully over several decades for the treatment of[unreadable] cancer and, more recently, HIV infection. However, the principles of treatment with multiple drugs which have[unreadable] distinct and additive or synergistic mechanisms of action and non-overlapping toxicity have not been applied to[unreadable] the treatment of sickle cell disease. The primary' hypothesis to be addressed in the Network (Inter-Center)[unreadable] Study is that combination treatment with hydroxyurea and magnesium will have a greater effect on the[unreadable] prevention of vaso-occlusive complications of sickle cell disease than treatment with hydroxyurea alone.[unreadable] Therefore, the Network Study will address Specific Aim 1: To determine the efficacy of combination[unreadable] treatment with hydroxyurea and magnesium compared to treatment with hydroxyurea alone on painful[unreadable] events and episodes of acute chest syndrome through Phase IIl trials in children and adults with sickle[unreadable] cell disease. Two separate, randomized double-blinded, multi-institutional trials of hydroxyurea and[unreadable] magnesium versus hydroxyurea and placebo will be conducted. Study I will enroll newly treated, symptomatic[unreadable] patients who meet the criteria for severe disease. Randomization to magnesium or placebo will occur after six[unreadable] months of hydroxyurea treatment during which time the maximal tolerated dose will be defined for each patient.[unreadable] Study II will enroll patients who have been previously treated with hydroxyurea for a minimum of 12 months[unreadable] but who remain symptomatic as reflected by the occurrence of a vaso-occlusive crisis within the 12 months prior[unreadable] to enrollment. Specific Aim 2: To measure splenic function by liver-spleen scan in patients treated on the[unreadable] Phase III trials prior to randomization and after two years of treatment. Little information is available[unreadable] with respect to the impact of drug therapy on spleen structure and function. By systematically collecting data,[unreadable] we will be able to compare the frequency of restoration of spleen function as reflected by the liver-spleen scan in children and adults treated with hydroxyurea alone or hydroxyurea and magnesium. At the completion of these[unreadable] Network (Inter-Center) trials, we will know whether the combination of hydroxyurea and magnesium is superior[unreadable] to hydroxyurea alone in the prevention of vaso-occlusive events and we will have preliminary information[unreadable] the frequency with which hydroxyurea or hydroxyurea/magnesium can restore splenic function.